4-Octyl Itaconate Attenuates Cell Proliferation by Cellular Senescence via Glutathione Metabolism Disorders and Mitochondrial Dysfunction in Melanoma

Antioxidants and Redox Signaling, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Aims: Itaconate (IA) is synthesized in the citric acid cycle via cis-aconitate decarboxylase (ACOD1); however, its biological significance cancer remains incompletely understood. In previous studies, 4-octyl itaconate (OI) was used as a membrane-permeable form of IA, but little detailed verification difference activities between IA and OI exists. Here, we investigated direct effects on melanoma. Results: The proliferation melanoma cells treated with significantly suppressed vitro, our transcriptomic analysis revealed drastic changes expression glutathione metabolism-related genes OI-treated cells. Indeed, treatment decreased intracellular levels, followed by increased production reactive oxygen species γH2AX, marker DNA damage, β-galactosidase, cellular senescence. We further showed that mitochondrial respiratory capacity B16 treatment. administration also growth tumor transplants vivo, γH2AX tissues mice. addition, minimal were observed melanocytes normal tissues. proved not only exogenous which enters intracellularly, endogenous has effect activity, an investigation using Acod1-overexpressing transfectants Acod1-deficient Conclusion: This work disrupts antioxidant system collapse metabolism inhibits cell proliferation. Antioxid. Redox Signal. 00, 000-000.

Language: Английский

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Bibliometric analysis of treatment modalities in calcific aortic valve stenosis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Background Calcific aortic valve stenosis (CAVS) is a common cardiovascular condition associated with significant adverse events and high mortality rates. Unfortunately, there are currently no effective pharmacological treatments to halt or prevent its progression. Through our analysis of global trends treatment strategies, we have identified valuable insights promising therapeutic possibilities. Additionally, by utilizing bibliometric visualization techniques, provide comprehensive overview the current research landscape in this field. Method According design idea, used Web Science database select publications on related treatments. VOSviewer CiteSpace analysis, total 787 articles been analyzed September 2024. We also summarize explore most prolific authors, countries, journals institutions that publish articles. Results A visual collected reveals Canada United States highest publication volumes Among institutions, Harvard University U.S. leads count, followed Laval California The top three hotspots stenosis, calcification, journal number area Frontiers Cardiovascular Medicine, Catheterization Interventions Arteriosclerosis, Thrombosis Vascular Biology. Furthermore, CAVS spans various directions focuses, including approaches, pathogenesis, diagnostic methods. Conclusion Research into has advanced significantly over years. While interventional surgical replacement remains mainstay for they insufficient fully meet needs patient. Emerging priorities now focus improving diagnostics, exploring innovative therapies, uncovering disease mechanisms, developing novel drugs. These findings highlight evolving demands field underscore need continued address these challenges.

Language: Английский

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Circulating PGC-1α and MOTS-c Peptide as Potential Mitochondrial Biomarkers in Patients Undergoing Aortic Valve Replacement

Biologics, Journal Year: 2025, Volume and Issue: Volume 19, P. 87 - 96

Published: March 1, 2025

Aortic valve disease (AVD) is a common condition that leads to pressure and/or volume overload in the left ventricle. replacement standard treatment, as no pharmacological therapies are currently available. The incidence of AVD increasing developed countries, making discovery new biomarkers for early detection crucial. importance mitochondria heart function well established, and various cardiovascular pathologies associated with mitochondrial dysfunction. In this cross-sectional study, we evaluated first time role AVD, aiming identify pathways involved discover potential biomarkers. We recruited 17 patients diagnosed scheduled aortic replacement, 22 healthy controls. Plasma levels peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) open reading frame 12S rRNA type-c peptide (MOTS-c) were measured by ELISA. observed significantly reduced both proteins patients, suggesting substantial dysfunction occurs independent sex or age, but directly related disease. Mitochondria may represent promising target studying AVD. propose PGC1α MOTS-c plasma detection. Further studies, including early-stage necessary confirm significance our findings.

Language: Английский

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The gut microbiota in mice with erythropoietin—induced abdominal aortic aneurysm

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e19222 - e19222

Published: April 7, 2025

Background In recent years, a novel animal abdominal aortic aneurysm (AAA) model was established by administering erythropoietin (EPO) to wild-type (WT) mice. However, the influence of EPO on murine fecal microbiota remains uninvestigated. Therefore, this study aims explore potential association between gut changes and AAA development in model. Methods results Adult male C57BL/6 mice were used establish intraperitoneal administration recombinant human at dosage 10,000 IU/kg daily for 28 consecutive days. Hematoxylin eosin (H&E) Elastin Van Gieson (EVG) staining revealed that increased wall thickness diameter, accompanied enhanced degradation elastic lamina. The 16S rRNA—sequencing data deposited Sequence Read Archive (PRJNA1172300). LEfSe analysis Akkermansia, Lawsonibacter, Clostridium, Neglectibacter significantly associated with EPO-induced development, while Lactobacillus, Alistipes, Limosilactobacillus, Eisenbergiella showed significant negative correlations. Analysis using Kyoto Encyclopedia Genes Genomes (KEGG) prediction module differences metabolic pathways two groups, including alanine, aspartate glutamate metabolism; cysteine methionine pyrimidine carbon ABC transporters; oxidative phosphorylation pathways. Conclusions dysbiosis, particularly Alistipes abundance, may contribute formation via inflammation, stress, dysfunction. While advances research, its limitations underscore need validation mechanistic studies. Future work should prioritize multi-omics integration cross-model comparisons unravel complex microbiota-AAA axis.

Language: Английский

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PM2.5 Induced Vascular and Myocardial Calcification Impairs Ischemia-reperfusion Tolerance via Mitochondrial Dysregulation

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Language: Английский

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